One cognitive function often taken for granted is the ability to maintain a sense of direction and location while moving about in the environment. This awareness is essential for getting around and functioning normally in the world. When our sense of spatial orientation is compromised by central nervous system or vestibular disease, the seriousness and devastation of the disorder becomes readily apparent both to the patient and clinician. Common problems include dizziness, balance, and spatial disorientation. To develop effective treatments for these disorders, we will need to understand the neural processes underlying spatial orientation and what goes awry with these processes that brings about disorientation. Thus, the long-term goal of this proposal is to better understand the neural mechanisms contributing to spatial perception of one's orientation. Using an animal model and electrophysiological techniques we will record from a class of neurons in rats that encodes the animal's directional heading in allocentric coordinates. These neurons are referred to as 'head direction (HD) cells' and have been identified in non-human primates. Our aim is to understand how head direction cells respond under a variety of conditions that pertain to issues of spatial orientation and disorientation. The experiments investigate 1) the response of HD cells in three dimensions - in particular, how they respond when the animal is inverted and locomotes upside-down while performing a spatial memory task, 2) the role of the vestibular system, both the semi-circular canals and the otolith organs, in generating HD cell responses, 3) the role of motor/proprioceptive cues in the discharge of angular head velocity cells, 4) the role of limbic system circuitry in generating head direction cell responses in the striatum, and 5) the response of HD cells during periods of disorientation. In sum, the results we obtain will provide essential information for understanding the neurophysiological basis for spatial orientation disorientation, and enhance our understanding of how spatial information is organized and processed in the mammalian brain. PUBLIC HEALTH RELEVANCE The results from these experiments will provide key information in understanding the basic neural mechanisms underlying spatial orientation. Ultimately, we would like to develop a better neurophysiological understanding of disorientation and use this information to develop effective treatments for spatial disorders such as vertigo, motion sickness, navigational disorders. Further, it is common for patients with vestibular disorders, elderly patients, and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will provide clues about the complex nature of spatial processes in humans. [unreadable] [unreadable] [unreadable]